title: A multicentre study of motor functional connectivity changes in patients with multiple sclerosis.
abstract: In this multicentre study involving eight European centres, we characterized the spatial pattern of functional connectivity (FC) in the sensorimotor network from 61 right-handed patients with multiple sclerosis (MS) and 74 age-matched healthy subjects assessed with the use of functional magnetic resonance imaging (fMRI) and a simple motor task of their right dominant hand. FC was investigated by using: (i) voxel-wise correlations between the left sensorimotor cortex (SMC) and any other area in the brain; and (ii) bivariate correlations between time series extracted from several regions of interest (ROIs) belonging to the sensorimotor network. Both healthy controls and MS patients had significant FC between the left SMC and several areas of the sensorimotor network, including the bilateral postcentral and precentral gyri, supplementary motor area, middle frontal gyri, insulae, secondary somatosensory cortices, thalami, and right cerebellum. Voxel-wise assessment of FC revealed increased connectivity between the left SMC and the right precentral gyrus, right middle frontal gyrus (MFG) and bilateral postcentral gyri in MS patients as compared with controls. ROI analysis also showed a widespread pattern of altered connectivity, characterized by increased FC between the right MFG, the left insula and the right inferior frontal gyrus in comparison with many regions of the sensorimotor network. These results provide further evidence for increased bihemispheric contributions to motor control in patients with MS relative to healthy controls. They further suggest that multicentre fMRI studies of FC changes are possible, and provide a potential imaging biomarker for use in experimental therapeutic studies directed at enhancing adaptive plasticity in the disease.
authors.affiliation: Division of Neuroscience, Neuroimaging Research Unit, Institute of Experimental Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Valsasina
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rocca
authors.forename: Martina
authors.initials: M
authors.lastname: Absinta
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.forename: Laura
authors.initials: L
authors.lastname: Mancini
authors.forename: Nicola
authors.initials: N
authors.lastname: De Stefano
authors.forename: Alex
authors.initials: A
authors.lastname: Rovira
authors.forename: Achim
authors.initials: A
authors.lastname: Gass
authors.forename: Christian
authors.initials: C
authors.lastname: Enzinger
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Christiane
authors.initials: C
authors.lastname: Wegner
authors.forename: Paul M
authors.initials: PM
authors.lastname: Matthews
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D009103:Multiple Sclerosis / Q000473:pathology / Q000503:physiopathology*; D009415:Nerve Net / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology*; D009434:Neural Pathways / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*